Most currently-available thermocyclers are so-called "block thermocyclers". Such block thermocyclers have contributed much to the success of polymerase chain reaction (PCR; Mullis, Mullis, et al.) by allowing users a simple, convenient, and repeatable method for temperature cycling reactions. They allow very large volume reactions for preparative work, though this often requires re-optimization of the cycling parameters since temperature control is usually done on the block temperature and not the sample temperature. Due to the large sample size, block thermocyclers are relatively slow, with even the best machines (e.g., Perkin-Elmer 9600) capable of a maximal throughput of less than 1500 reactions per day. Further, block thermocyclers are typically among the most expensive in terms of per-sample reagent costs is (the Perkin-Elmer 9600 costs about $4.00 per sample).
Corbett, et al., describe a continuous serial-flow thermal cycler having a single long capillary tube wound around heating elements maintained at different temperatures. Different samples are serially passed through the same tube. The invention suffers from the disadvantages of potential sample contamination by residue left from a previous bolus, and inability to independently vary the dwell time or temperature for different samples.
Accordingly, a need exists for a rapid, efficient thermocycler. The present invention provides such a thermocycler--an apparatus capable of rapid amplification of small volume DNA samples, with minimal potential for cross-over contamination and capacity for independent regulation of the cycling parameters for each sample, at a per-sample reagent cost of less than $0.20.